1. Field of Invention
The present invention relates generally to an apparatus and a method of producing solid-lipid composite drug particles.
2. Description of Related Art
In recent years, solid composite lipid/drug particles have been used for oral, pulmonary and parenteral drug delivery as an alternative to traditional drug delivery systems such as emulsions, liposomes and biodegradable polymer nanoparticles. Solid lipid/drug composite particles provide the advantages of traditional drug delivery systems, such as improved dissolution and controlled release, but avoid some of the disadvantages of traditional drug delivery systems. The use of drug-containing emulsions, for example, is limited by the physical stability of the drug-containing emulsions, and also by the low dissolution of most drugs in the triglycerides used to form the emulsions. Liposome based drug delivery systems are limited by the non-availability of inexpensive pharmaceutical liposomes, and also by the low solubility of most drugs in the liposome membrane. Biodegradable polymer nanoparticles are limited by the cytotoxicity of certain polymers in the human body.
Most lipids are well tolerated by the human body and do not cause undesirable side effects upon delivery. Thus, they are particularly suitable for use in delivering drugs. Conventional methods of making solid composite lipid/drug particles include: the high-pressure homogenization process, which is described by Lucks et al. in EP 0 605 497; the microemulsion process, which is described by Gasco in U.S. Pat. No. 5,250,236; the precipitation process, which is described by Siekmann and Westesen in Preparation And Physicochemical Characterization Of Aqueous Dispersions Of Coenzyme Q10 Nanoparticles, Pharm Res. 1995; 12:201-208; and the nanopelletization process, which is described by Domb in U.S. Pat. No. 5,188,837.
There are some inherent limitations on the conventional methods of forming solid composite lipid/drug particles. The high-pressure homogenization process, for example, is limited by the solubility of the drug in the molten lipid, and cannot be used to effectively produce solid composite lipid/drug particles having an average particle diameter of less than 100 nm. The average particle size of solid composite lipid/drug particles produced via the microemulsion process tends to be quite small, but the dispersion obtained using this process is extremely dilute and is thus not suitable for drug delivery applications. And, although the precipitation process can be used to produce fine particles having average diameters in the nanometer range, large processing times are required in order to achieve low residual solvent content. Scale up of the process is also problematic.